Malignant tumors are a leading cause of death in modern societies. Photodynamic therapy (PDT) has been used for more than 100 years to treat tumors, and sonodynamic therapy has been very recently developed. With appropriate sensitizers, both have high efficacy, high selectivity and low side effects. There are good prospects of their wide clinical application (see Li Jian et al., Chinese Journal of Biomedical Engineering. 2005, 24:237-239; Thomas J., et al, Journal of the National Cancer Institute, 1998, 90: 889-905; Ionel Rosenthal et al, Ultrasonics Sonochemistry, 2004, 11: 349-336).
PDT is carried out in two steps: initially injecting or administering orally a photosensitive agent to a patient, and then activating the photosensitive agent by exposing the patient to light at an appropriate wavelength to produce “singlet oxygen”, thereby killing abnormal cells and microorganisms (see Moan J. et al, Photochem. Photobiol. 1991; 53: 549-553). Since the photosensitive agent administered is specifically concentrated in abnormal cells, such as cancer cells, the therapy is effective in destroying these cells with minimal damage to normal cells (see Thomas J., et al, Journal of the National Cancer Institute, 1998, 90: 889-905; Musser D. A. et al, Res. Commun. Chem. Pathol. Pharmacol. 1980; 28:505-525). It is particularly effective in treating early-stage and superficial tumors, with an efficacy of 84-100% [Hopper C. et al. Int. J Cancer. 2004, 111(1):138-146; Kato H. et al. Lung Cancer. 2003, 42:103-111; Mang T. S. et al. Cancer J Sci. Am.; 1998, 4:378-84].
PDT, however, has three main disadvantages. Firstly, since the red light, usually used therein, penetrates the human body only to a depth of up to 10 mm, PDT is only used to treat tumors occurring in very superficial or topical areas (see Thomas J., et al, Journal of the National Cancer Institute, 1998, 90: 889-905). Secondly, since the currently available photosensitive agents are metabolized at a low speed in normal cells, after treatment, patients must be protected from light for a period of 30 days, to prevent photosensitive dermatitis (see Li Jian, Chinese Journal of Biomedical Engineering, 2005, 24:237-239). Thirdly, PDT typically requires an interventional procedure to introduce optical fibers into the body or tumor, thus increasing pain and risk for patients (see Kato H. et al, Lung Cancer. 2003, 42(1):103-111).
Sonodynamic therapy has been developed as a therapy complementary or alternative to PDT. It treats cancers with ultrasound and sound-sensitive agents (see Joe Z., et al., Ultrasonics Sonochemistry, 2004, 11: 349-336). The mechanism is that the ultrasounds activate the sound-sensitive agent in body to produce singlet oxygen, thus killing abnormal cells such as tumor cells (see Kuroki M. et al,. 2007, Anticancer Res. 27:3673-3677). A synergistic effect may be observed if SDT is combined with chemotherapy or PDT (see Jin Z H et al, J Dermatol, 2000, 27: 294-306; Ionel Rosenthal et al., Ultrasonics Sonochemistry, 2004, 11: 349-336). Clinical applications of SDT, however, have not been reported, not least because no suitable sound-sensitive agents are available that are both specifically enriched in focal areas and sufficiently high sound-sensitive to produce singlet oxygen, which kills abnormal cells such as tumor cells.
Porphyrin compounds have been known to serve as photosensitive and sound-sensitive agents. They selectively adhere to abnormal cells such as tumor cells (see Yao J Z et al., Chin J Pharmaceuticals 2000; 31: 2157; Liu H L et al., Chin J Laser Med Surg 2002; 11: 889; Umemura K et al., Cancer Lett., 1996, 102: 151-157; Yumita N et al., Cancer Science, 2008, 99: 166-172). In the case of SDT, however, no satisfactory sound-sensitive agents and thus suitable therapies are available for clinical application at present.